Han Young Sang, Lee Ji Eun, Jung Ji Won, Lee Jong Soo
Department of Ophthalmology, College of Medicine, Pusan National University, Seo-Ku, Pusan 602-739, Korea.
Graefes Arch Clin Exp Ophthalmol. 2009 Apr;247(4):541-8. doi: 10.1007/s00417-008-0976-3. Epub 2008 Oct 25.
To evaluate the inhibitory effects of bevacizumab (Avastin) on angiogenesis using cultured human umbilical vein endothelial cells (HUVECs) in vitro and on corneal neovascularization by subconjunctival injection of bevacizumab in vivo.
After the HUVECs were exposed to different concentrations of bevacizumab stimulated with VEGF (10 ng/ml) for 2, 6, and 24 hours, cellular-activity-like proliferation, migration and tube formation were assessed. Subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) was performed after corneal chemical burn injury. Then the cornea was evaluated by biomicroscopy, fluorescein angiography, and light microscopy.
The inhibitory effects of bevacizumab on VEGF-induced HUVECs proliferation showed a dose-dependent response for 2 and 6 hours, but all groups were effectively inhibited regardless of the concentration of bevacizumab for 24 hours. The inhibitory effects of bevacizumab on the migration of VEGF-induced HUVECs showed a time- and dose-dependent response. The inhibitory effects of bevacizumab on VEGF-induced HUVECs tube formation showed a dose-dependent response only for 24 hours. On days 3 and 8 after the subconjunctival injection, bevacizumab-treated eyes showed less neovascular growth than BSS-treated eyes in biomicroscopic, fluorescein angiographic, and light microscopic findings in vivo.
Bevacizumab effectively inhibits angiogenesis and corneal neovascularization, and could be used as a inhibitor of corneal neovascularization in the future.
体外使用培养的人脐静脉内皮细胞(HUVECs)评估贝伐单抗(阿瓦斯汀)对血管生成的抑制作用,并通过在体内结膜下注射贝伐单抗评估其对角膜新生血管形成的作用。
将HUVECs暴露于不同浓度的贝伐单抗,并在VEGF(10 ng/ml)刺激下培养2、6和24小时,然后评估细胞活性样增殖、迁移和管腔形成。在角膜化学烧伤损伤后进行结膜下注射贝伐单抗(2.5 mg/0.1 ml)。然后通过生物显微镜检查、荧光素血管造影和光学显微镜对角膜进行评估。
贝伐单抗对VEGF诱导的HUVECs增殖的抑制作用在2和6小时呈剂量依赖性反应,但在24小时时,无论贝伐单抗浓度如何,所有组均受到有效抑制。贝伐单抗对VEGF诱导的HUVECs迁移的抑制作用呈时间和剂量依赖性反应。贝伐单抗对VEGF诱导的HUVECs管腔形成的抑制作用仅在24小时呈剂量依赖性反应。在结膜下注射后的第3天和第8天,在体内生物显微镜检查、荧光素血管造影和光学显微镜检查中,接受贝伐单抗治疗的眼睛比接受平衡盐溶液(BSS)治疗的眼睛新生血管生长更少。
贝伐单抗可有效抑制血管生成和角膜新生血管形成,未来可作为角膜新生血管形成的抑制剂使用。